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1.
The immunoregulatory signaling (IRS) family includes several molecules, which play major roles in the regulation of the immune response. The CMRF-35A and CMRF-35H molecules are two new members of the IRS family of molecules, that are found on a wide variety of haemopoietic lineages. The extracellular functional interactions of these molecules is presently unknown, although CMRF-35H can initiate an inhibitory signal and is internalized when cross-linked. In this paper, we described the gene structure for the CMRF-35A gene and its localization to human chromosome 17. The gene consists of four exons spanning approximately 4.5 kb. Exon 1 encodes the 5' untranslated region and leader sequence, exon 2 encodes the immunoglobulin (Ig)-like domain, exon 3 encodes the membrane proximal region and exon 4 encodes the transmembrane region, the cytoplasmic tail and the 3' untranslated region. A region in the 5' flanking sequence of the CMRF-35A gene, that promoted expression of a reporter gene was identified. The genes for the CMRF-35A and CMRF-35H molecules are closely linked on chromosome 17. Similarity between the Ig-like exons and the preceding intron of the two genes suggests exon duplication was involved in their evolution. We also identified a further member of the CMRF-35 family, the CMRF-35J pseudogene. This gene appears to have arisen by gene duplication of the CMRF-35A gene. These three loci - the CMRF-35A, CMRF-35J and CMRF-35H genes-form a new complex of IRS genes on chromosome 17. 相似文献
2.
Human CD38 is a 45-kDa type II membrane glycoprotein with an intricate pattern of expression in leukocytes, although evidence is accumulating of its quite widespread expression in cells of nonvascular origin. CD38 is a member of a nascent eukaryotic gene family encoding cytosolic and membrane-bound enzymes whose substrate is NAD, a coenzyme ubiquitously distributed in nature. Functionally, CD38 is an eclectic molecule with the ability not only to catalyze but also to signal, to mobilize calcium, and to adhere to itself, to hyaluronan, and to other ligands. Interaction with CD38 on various leukocyte subpopulations has profound though diverse consequences on their life-span, but these effects seem to be independent of the enzymatic activity of the molecule. CD38 challenges our expectations of a surface molecule and we must sift through its many guises to unmask its true nature. 相似文献
3.
The expression of membrane immunoglobulin (mIg) was examined in three cloned MPC11-derived mouse myelom a cell lines. Membrane immunofluorescence studies demonstrated that IgG2b producer cells (P1) had complete IgG molecules, L-chain producer (L1) had only L-chain determinants and nonproducer (NP2) did not have any Ig determinants on the cell surface. An Ig receptor, with characteristics different from B lymphocyte Fc receptor, has been found to be present on secreting cells (P1 or L1), but not on the NP2 cell variant. The data reported in the present paper indicate that the expression of mIg and of the Ig receptor molecule is clearly correlated with the process of secretion. In the light of previous data reported on Ig secretion, a model is proposed which correlates the process of secretion with the expression not only of mIg, but also of the receptor for Ig. 相似文献
4.
Bovine pan T-cell monoclonal antibodies reactive with a molecule similar to CD2. 总被引:4,自引:0,他引:4
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Monoclonal antibodies (mAb) CH128A and CH61A react with molecules of 50,000-60,000 MW. They are expressed by all T cells in cattle, comprising 44-69% of peripheral blood mononuclear leucocytes (PBM), the majority of lymphocytes in T-dependent areas of lymph node, and 75-80% of cells derived from the thymus including both cortical and medullary thymocytes. The molecule recognized by these mAbs is not expressed on B lymphocytes, monocytes/macrophages, or granulocytes. Both mAb inhibit spontaneous rosette formation by sheep erythrocytes and bovine lymphocytes. We postulate that these mAb see the bovine homologue of the human sheep red blood cell receptor CD2 and has been named BoT2. 相似文献
5.
R Prades S Guerrero E Araya C Molina E Salas E Zurita J Selva G Egea C López-Iglesias M Teixidó MJ Kogan E Giralt 《Biomaterials》2012,33(29):7194-7205
The treatment of Alzheimer's disease and many other brain-related disorders is limited because of the presence of the blood-brain barrier, which highly regulate the crossing of drugs. Metal nanoparticles have unique features that could contribute to the development of new therapies for these diseases. Nanoparticles have the capacity to carry several molecules of a drug; furthermore, their unique physico-chemical properties allow, for example, photothermal therapy to produce molecular surgery to destroy tumor cells and toxic structures. Recently, we demonstrated that gold nanoparticles conjugated to the peptide CLPFFD are useful to destroy the toxic aggregates of β-amyloid, similar to the ones found in the brains of patients with Alzheimer's disease. However, nanoparticles, like many other compounds, have null or very low capacity to cross the blood-brain barrier. In order to devise a strategy to improve drug delivery to the brain, here we introduced the peptide sequence THRPPMWSPVWP into the gold nanoparticle-CLPFFD conjugate. This peptide sequence interacts with the transferrin receptor present in the microvascular endothelial cells of the blood-brain barrier, thus causing an increase in the permeability of the conjugate in brain, as shown by experiments in?vitro and in?vivo. Our results are highly relevant for the therapeutic applications of gold nanoparticles for molecular surgery in the treatment of neurodegenerative diseases such as Alzheimer's disease. 相似文献
6.
The paired box encodes a second DNA-binding domain in the paired homeo domain protein. 总被引:30,自引:0,他引:30
The homeo box, which encodes the DNA-binding homeo domain, is a DNA sequence motif present in several Drosophila developmental genes; it has been used to identify many homologous genes involved in mammalian development. The paired box is another conserved sequence motif, first identified in the paired (prd) and gooseberry (gsb) Drosophila homeo domain genes. It encodes a 128-amino-acid domain, the paired domain, which has since been found in other fly and mouse gene products, in association with the homeo domain or in its absence. We show that the paired box of the prd gene encodes a DNA-binding activity, independent of the DNA-binding activity of the Paired (Prd) homeo domain and with a different sequence specificity. The amino-terminal region of the paired domain, including one of the three predicted alpha-helices, is necessary and sufficient for binding. We investigate the binding of the Prd protein to two sites in the even-skipped promoter, which are composed of overlapping sequences bound by the homeo domain and by the paired domain. We also show that a mutation in the paired box of Prd, corresponding to the mutation in the paired box of the mouse Pax-1 gene thought to cause the undulated skeletal phenotype, destroys the ability of the Prd protein to bind to the paired domain-specific site. This supports the view that the undulated phenotype results from the inactivation of the DNA-binding activity of the paired domain of Pax-1. 相似文献
7.
We have recently identified a novel murine glycoprotein termed sgp-60, which is expressed on the cell surface of T and B lymphocytes. Because of the profound modulatory effects of sgp-60 on activation through the T cell receptor/CD3 complex, we have examined the membrane attachment domain of the molecule. sgp-60 is not expressed on the surface of variants of a T-T hybridoma cell line that are defective in glycosylphosphatidylinositol (GPI) anchor biosynthesis. In wild-type but not in mutant cells, sgp-60 can be labeled with palmitic acid. Furthermore, the molecule can be removed from the cell surface of both T and B lymphocytes by enzymatic digestion with a phosphatidylinositol-specific phospholipase C. We conclude that the sgp-60 molecule is linked to the plasma membrane via a GPI anchor. 相似文献
8.
The distal pole complex: a novel membrane domain distal to the immunological synapse 总被引:3,自引:1,他引:2
Summary: While much interest has focused on the finding that T cell–antigen presenting cell (APC) interaction induces the recruitment of proteins to the immunological synapse (IS), we have recently discovered that APC binding induces the formation of a novel protein complex distal to the site of T‐cell receptor ligation. This ‘distal pole complex’ (DPC) is important for appropriate T‐cell activation, functioning either to remove proteins from the synapse or as a signaling complex in its own right. The first component of the DPC to be identified was CD43, a cell‐surface mucin that has been proposed to function as a negative regulator of T‐cell signaling. CD43 movement was found to depend on ezrin and moesin, members of the ERM family, which serve to link CD43 and other cargo molecules to the actin cytoskeleton. ERM proteins interact with several other important surface receptors and cytoplasmic signaling molecules, some of which we have identified as additional components of the DPC. Disruption of the DPC leaves early T‐cell activation events intact but affects cytokine expression. Here, we review what is currently known about the formation and function of the DPC and speculate on how this novel protein complex serves to facilitate T‐cell activation. 相似文献
9.
Najet Rebai Bernard Malissen Michel Pierres Roberto S. Accolla Giorgio Corte Claude Mawas 《European journal of immunology》1983,13(2):106-111
A series of HLA-DR-reactive mouse anti-human B cell or anti-Ia monoclonal antibodies (mAb) have been used to explore the serological complexity of human class II antigens at the determinant level, using two techniques: (a) cross antibody-binding competitor assays using 125I-labeled and -unlabeled mAb were performed to study the topological organization of the corresponding determinants to determine epitopic clusters recognized by this collection of mAb and (b) differential reactivity of mAb to detergent-solobilized solid-phase-immobilized HLA-DR molecules to determine epitopes expressed on identical DR isotypes. The fifteen mAb could be classified according to the first technique as falling into three different epitopic clusters. Using the second technique, we were able to define at least two independent molecular subsets, one co-expressing two of the three epitopic clusters and the second expressing only the third one. We could not formally identify molecular subsets expressing only one of the first two clusters, using the second technique. The precise serological mapping of the determinants recognized by various anticlass II mAb should prove very useful if such mAb were to be introduced in anticlass II-specific T cell clone blocking experiments. We anticipate that some of them should facilitate the correlation at the clonal level between the T cell repertoire and the epitopes or molecular subsets defined by these mAb. However, within mAb belonging apparently to a same cluster, some could mediate different biological effects. 相似文献
10.
11.
A mouse anti-rat interleukin 2 (IL 2) receptor (IL 2R) monoclonal antibody (mAb), ART-65, has been developed. As shown by fluorescence-activated cell sorter analysis and immunoprecipitation studies, ART-65 recognizes in a species-specific manner the same molecule as does ART-18, a mAb which has been shown previously to recognize the rat receptor for IL 2. ART-65 and ART-18 do not competitively inhibit the binding of each other to activated T cells. ART-65, in contrast to ART-18, does not inhibit the binding of IL 2 to cells nor does it have any inhibitory effect in vitro on IL 2-driven proliferation of rat T lymphoblasts. Therefore, ART-65 is another mAb recognizing the rat IL 2 receptor, but binding to an epitope distinct from that recognized by either IL 2 or ART-18. We compared the in vivo activity of the mAb ART-65 and ART-18 with that of the W3/25 mAb in a local graft-vs-host reaction (GVHR). Similar to the anti-W3/25 treatment, ART-65 and ART-18 inhibited GVHR. The results demonstrate that GVHR depends on a small subpopulation of IL 2R+ cells present in the W3/25+ T cell population because IL 2R-targeted therapy was as effective as the treatment with W3/25 mAb which reacts with the entire T helper cell population. Moreover, the results argue against the possibility that anti-IL 2R mAb act via blockade of the IL 2 binding to IL 2R+ cells and/or by inhibiting the IL 2-driven expansion of the antigen-activated clones. The results support the view that IL 2R-targeted therapy results in the elimination of the IL 2R+ cells. 相似文献
12.
The C domain in the surface envelope glycoprotein of subgroup C feline leukemia virus is a second receptor-binding domain 总被引:1,自引:0,他引:1
The receptor-binding domain (RBD) in the surface (SU) subunit of gammaretrovirus envelope glycoprotein is critical for determining the host receptor specificity of the virus. This domain is separated from the carboxy terminal C domain (Cdom) of SU by a proline-rich region. In this study, we show that the Cdom region in the SU from subgroup C feline leukemia virus (FeLV-C) forms a second receptor-binding domain that is distinct from its RBD, and which can independently bind to its host receptor FLVCR1, in the absence of RBD. Furthermore, our results suggest that residues located in the C2 disulfide-bonded loop in FeLV-C Cdom are critical for SU binding to FLVCR1 and for virus infection. We propose that binding of FeLV-C SU to FLVCR1 involves interaction of two receptor-binding domains (RBD and Cdom) with FLVCR1, and that this mechanism of interaction is conserved for other gammaretroviruses. Our results could have important implications for designing gammaretrovirus vectors that can efficiently infect specific target cells. 相似文献
13.
14.
Bucheton B Argiro L Chevillard C Marquet S Kheir MM Mergani A El-Safi SH Dessein AJ 《Genes and immunity》2007,8(1):79-83
Binding of the interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) triggers a series of intracellular events culminating in lymphocyte proliferation and differentiation. We report here the identification of a novel G245R polymorphism in the membrane proximal domain of the IL-2 receptor beta chain (IL-2Rbeta). Present at a frequency of 7.2%, the IL-2-Rbeta G245R was identified in a population of Eastern Sudan exposed to a severe outbreak of visceral leishmaniasis (VL), a disease associated with a marked depression of T-cell antigen-specific responses. The location of the G245R polymorphism next to the box1/box2 proximal cytokine receptor homology segment and suggestive genetic association with the development of disease (P=0.043), suggest that it may affect Janus kinase (JAK) association and impair growth signal transduction. However, additional genetic association with a synonymous single nucleotide polymorphism (IL2RB+8777T) suggests that other variations of IL2RB or nearby genes participate in the highly significant linkage with VL at 22q12 previously reported for this population. 相似文献
15.
Ig/EBP-1: a ubiquitously expressed immunoglobulin enhancer binding protein that is similar to C/EBP and heterodimerizes with C/EBP 总被引:45,自引:0,他引:45
We report the isolation and characterization of cDNA clones that encode a protein with the same DNA binding specificity as the immunoglobulin heavy chain enhancer binding protein E (muEBP-E). We call the gene encoding this protein Ig/EBP-1. A fusion protein encoded by the cDNA binds specifically to muEBP-E-binding sites (E sites) in both the IgH enhancer and the VH1 promoter. Sequence analysis reveals that Ig/EBP-1 is a member of the "basic-zipper" family of DNA-binding proteins that are characterized by basic regions and heptad repeats of leucine residues. Among known family members, Ig/EBP-1 demonstrates highest homology to C/EBP throughout the DNA-binding domain and leucine repeat region. Ig/EBP-1 and C/EBP have highly overlapping binding specificities; both cloned proteins bind to the IgH enhancer and the VH1 promoter E sites, and Ig/EBP-1 binds to previously characterized C/EBP binding sites in the Rous sarcoma virus (RSV) LTR and the murine albumin promoter. Consistent with their homology in the leucine repeat region, Ig/EBP-1 and C/EBP form heterodimers; Ig/EBP-1 is the first member of this family that has been found to heterodimerize with the well-characterized C/EBP. Ig/EBP-1 mRNA is present in all tissues and cell lines examined, although its levels vary almost 20-fold from different sources, with highest levels in early B cells. In tissues where Ig/EBP-1 and C/EBP are both present, heterodimers may be functionally important. The presence of Ig/EBP-1 in fibroblasts and other tissues where C/EBP is not expressed suggests that Ig/EBP-1 may be functionally important for the activity of the RSV enhancer in these cell types. Finally, elevated expression of Ig/EBP-1 in early B cells may explain in part the enhancer-independent activity of VH promoters early in B-cell development. 相似文献
16.
Guiraldelli MF Berenstein EH Grodzki AC Siraganian RP Jamur MC Oliver C 《Molecular immunology》2008,45(8):2411-2418
The mast cell specific monoclonal antibody, mAb BGD6, is a mast cell lineage marker [Jamur, M.C., Grodzki, A.C., Berenstein, E.H., Hamawy, M.M., Siraganian, R.P., Oliver, C., 2005. Identification and characterization of undifferentiated mast cells in mouse bone marrow. Blood 105, 4282-4289]. In rat basophilic leukemia (RBL-2H3) cells, mAb BGD6 precipitates cell-surface proteins of approximately 110 and 40-60 kDa. An expression cloning strategy was used to identify proteins that interact with mAb BGD6. A RBL-2H3 cDNA library in plasmids was transfected into PEAK cells, which do not bind mAb BGD6, and positive cells were selected with mAb BGD6. The plasmids recovered from the positive cells were amplified; retransfected into PEAK cells and after several screening cycles a positive clone was identified. This clone showed almost complete identity to Fc gamma RIIB (CD32), the low affinity IgG receptor. However, in contrast to the sequence in GenBank, this clone had an insert of 141 bp which codes for a longer isoform of this molecule with an extra 47 aa in its cytoplasmic domain. In RBL-2H3 cells both isoforms were expressed, with higher expression of the shorter form. The mechanism of binding of mAB BGD6 on both RBL-2H3 and CD32 transfected PEAK cells was then examined. Intact mAb BGD6 bound to both RBL-2H3 and CD32 expressing PEAK cells, but F(ab')(2) fragments bound only to RBL-2H3 cells demonstrating that mAb BGD6 binds to Fc gamma RIIB only through its Fc portion. On RBL-2H3 cells, the Fab of an anti-CD32 mAb partially inhibited the binding of intact mAb BGD6. The binding pattern of mAb BGD6 inhibited with anti-CD32 resembled that of the F(ab')(2) fragment of the antibody suggesting that the Fc portion of mAb BGD6 contributes to its binding on cells that have Fc gamma RIIB. These results are consistent with a model where mAb BGD6 binds through its Fab portion to a approximately 110 kDa protein and the Fc tail interacts with Fc gamma RIIB (CD32). 相似文献
17.
Gaffar FR Yatsuda AP Franssen FF de Vries E 《Molecular and biochemical parasitology》2004,136(1):25-34
Recognition and invasion of host cells is a key step in the life-cycle of all apicomplexan parasites. The thrombospondin-related anonymous protein (TRAP) of Plasmodium sporozoites is directly involved in both processes and shares conserved adhesive domains with micronemal transmembrane proteins of other apicomplexans. Here, we report the cloning and characterization of a Babesia bovis TRAP homologue (BbTRAP). It was predicted to be a type 1 transmembrane protein containing a von Willebrand Factor A domain (vWFA), a thrombospondin type 1 domain (TSP1), a conserved transmembrane region and a conserved cytoplasmic C-terminus, thus resembling the domain arrangement of Plasmodium TRAP. In contrast to Plasmodium TRAP, BbTRAP was shown to be present during the asexual erythrocytic cycle, being located mainly at the apical side of merozoites. Polyclonal rabbit antisera directed against synthetic peptides derived from the TSP1 domain or the C-terminal end of the ectodomain were shown to inhibit erythrocyte invasion in vitro. Both antisera recognized a 75 kDa protein in merozoite extracts as well as in a protein fraction that was secreted into the extracellular milieu during in vitro invasion of erythrocytes. 相似文献
18.
The glucocorticoid receptor recognizes a specific nucleotide sequence in hepatitis B virus DNA causing increased activity of the HBV enhancer 总被引:10,自引:0,他引:10
R Tur-Kaspa Y Shaul D D Moore R D Burk S Okret L Poellinger D A Shafritz 《Virology》1988,167(2):630-633
The hepatitis B virus (HBV) genome contains a specific DNA binding site for the glucocorticoid receptor. Using DNase I footprinting, this binding site was localized at HBV map positions 341-370 clockwise from the EcoRI site. The DNA sequence protected in the footprint contains two tandem copies of the GRE core hexanucleotide 5'-TGTTCCT-3'. Deletion analysis and reconstruction experiments in plasmid expression vectors demonstrated that this glucocorticoid receptor binding sequence serves as a signal for augmenting glucocorticoid-dependent activity of the HBV enhancer, which is located approximately 730 nucleotides downstream in the HBV genome. Even though it does not serve as an independent enhancer element, the HBV glucocorticoid receptor domain can therefore be categorized as a functional GRE. 相似文献
19.
CD5 is a member of a superfamily of proteins which contain one or more extracellular domains homologous to the type I macrophage Scavenger Receptor cysteine-rich (SRCR) domain. The extracellular region of CD5 is composed of three SRCR domains (D1, D2, D3). Murine CD5 (mCD5) is polymorphic (Ly-1. 1 and Ly-1. 2 alleles), however, the only murine CD5 gene characterized to date encodes the Ly-1. 2 allele (mCD5. 2). Likewise, the domain specificity of many of the available anti-mCD5 mAb recognizing either Ly-1. 1 or Ly-1. 2 or both has not been examined. Herein we describe the isolation and characterization of cDNA encoding the Ly1. 1 allele (mCD5. 1) and map the location and molecular nature of the mCD5 allelic variation. We also determined which SRCR domain of mCD5 is recognized by a panel of anti-mCD5 mAb. The mCD5.1 protein differs from mCD5.2 in only three amino acids, all of which map to the most amino terminal SRCR domain (D1) of mCD5. An additional seven silent substitutions were observed in the nucleotide sequence encoding mCD5 D1, D2 and transmembrane domains. Immunoglobulin (Ig) fusion proteins consisting of various combinations of mCD5. 1 or mCD5. 2 SRCR domains were produced and used to determine that allele specific mAb bound to D1, confirming sequence data. MAb against monomorphic determinants on mCD5 bound to each mCD5D1Ig. 相似文献